Microglial activation in early Alzheimer trajectory is associated with higher gray matter volume.

Abstract

To investigate the influence of microglial activation in the early stages of Alzheimer's disease trajectory, we assessed the relationship between microglial activation and gray matter volume and hippocampal volume in patients with mild cognitive impairment (MCI). In this study, 55 participants (37 with early stages of MCI and 18 controls) underwent [¹¹C]PBR28 PET, a marker of microglial activation; volumetric MRI to evaluate gray matter and hippocampal volumes as well as clinical and neuropsychometric evaluation. [¹¹C]PBR28 V_T (volume of distribution) was calculated using arterial input function and Logan graphical analysis. Gray matter volume and hippocampal volumes were calculated from MRI for each participant. Statistical parametric mapping software was used to perform voxel-wise correlations and biological parametric mapping analysis. Amyloid status was assessed using [¹⁸F]flutemetamol PET. Higher [¹¹C]PBR28 V_T in different cortical areas correlated with higher gray matter volume in both amyloid-positive and -negative MCI. In addition, higher hippocampal volume correlated with higher cortical [¹¹C]PBR28 Logan V_T. In this in vivo study, we have demonstrated that microglial activation quantified using [¹¹C]PBR28 PET was associated with higher gray matter volume and higher hippocampal volume in patients with MCI. This might suggest that microglial activation may not always be associated with neuronal damage, and indeed it may have a beneficial effect in the early stages of the Alzheimer trajectory. While further longitudinal studies are necessary, these findings have significant implications on therapeutic strategies targeting microglial activation.